Alpha-(2, 4, 6-triiodophenoxy) butyric acid and its preparation



United States Patent C(-(2,4,6-TRHODOPI'IENOXY)BUTYRIC ACID AND ITS PREPARATION Joseph Redel and Jacques Maillard, Paris, France, as-

signors to Chimie et Atomistique, Paris, France, a French body corporate No Drawing. Application January 26, 1954, Serial No. 406,359

Claims priority, application France August 7, 1953 8 Claims. (Cl. 260-521) The present invention has for object to provide, as a new product, a chemical compound: u(2,4,6-triiodophenoxy) butyric acid of formula This compound, which melts at 124-125 C., is of use particularly in cholecystography, i. e. as an agent for rendering the gall-bladder opaque for X-ray examination. It is only very slightly toxic and has the particularly useful property of rendering opaque in a remarkable manner not only the gall-bladder but also the bile ducts. It is moreover, under the conditions of use, well tolerated by the organism, as has been demonstrated by many experiments. All these properties are rarely united in one compound; the new compound according to the invention is therefore of particular interest in its application in cholecystography.

The invention also has for object to provide a process of preparing this compound which is characterized in that it comprises the steps of condensing 2,4,6-triiodophenol with an tat-halogenated butyric acid ester such asethyl a-bromobutyrate, in the presence of an alkaline alcoholate, such as sodium ethylate, and thereafter saponifying the a(2,4,6-triiodophenoxy) butyric acid ester thus obtained.

The condensation may be diagrammatically expressed thus:

I r rO-on nloMe IQOMB R103 1 IQ-OMe x-on-oo o R 1 rO-o-on-w o o R MeX I JJIHB Example To a solution of sodium ethylate, prepared with 2.80 g. 7

(0.12 at. g.) of sodium in 50 cc. absolute alcohol, there are added 47.20 g. (0.10 mol) of triiodophenol and, while stirring and maintaining the mixture at a slow boil, 24.50 g. (0.13 mol.) of ethyl a-bromobutyrate drop by drop over a period of 1 hour. The mixture is refluxed for 3 hours. The mixture is cooled and there is added thereto a large volume of ice water which dissolves the precipitated sodium bromide and separates the ester in the form of an oil which is extracted with ether. The ethereal solution is washed with ice water, containing 5% sodium hydroxide which removes the remaining traces of triiodophenorl, washed with water, dried and evaporated; the residue is heated in a vacuum in a water-bath so as to evaporate oif the excess brominated ester.

The raw ester is thereafter saponified by refluxing for 1 hour with cc. of 5% alcoholic sodium hydroxide solution. The cooled solution is greatly diluted and acidified by 10% hydrochloric acid. The semi-crystalline oil which separates out is extracted with ether and the solution is separated, washed with water and dried over anhydrous sodium sulfate. The ethereal solution is concentrated in the water-bath and petroleum ether is added thereto until a cloud appears; the product crystallizes at 0 C. After recrystallization in an ether-petroleum ether mixture or ethyl acetate-petrol ether mixture the pure acid melts at l24l25 C. Weight: 30 to 31g. Yield: 54 to 55%.

It should be understood that the invention is not limited to the mode of carrying out the invention hereinbefore described, which has been given merely by way of example, and changes and modifications may be made therein that fall within the scope of the appended claims.

Having now described our invention what we claim as new and desire to secure by Letters Patent is:

1. a-(2,4,6-triiodophenoxy) butyric acid.

2. As a new compound, of use particularly in cholecystography: a(2,4,6-triiodophenoxy) butyric acid of the 3. Process of preparing a(2,4,6-triiodophenoxy) butyric acid comprising the steps of condensing 2,4,6-triiodophenol with an int-halogenated butyric acid ester in the presence of an alkaline alcoholate and thereafter saponifying the u(2,4,6-triiodophenoxy) butyric acid ester thus obtained.

4. Process as claimed in claim 3, wherein the ot-halogenated butyric acid ester is ethyl ot-bromobutyrate.

5. Process as claimed in claim 3, wherein the alkaline alcoholate is sodium ethylate.

6. Process as claimed in claim 3, wherein the condensation is effected by refluxing the reactants in an alcohol identical to that entering into the composition of the alcoholate.

7. Process of preparing ot(2,4,6-triiodoplrenoxy) butyric acid comprising the steps of condensing 2,4,6- triiodophenol with ethyl ot-bromobutyrate in the presence of sodium ethylate and thereafter saponifying the a(2,4,6- triiodophenoxy) butyric acid ester thus obtained.

8. Process as claimed in claim 7, wherein the condensation is effected by refluxing the reactants in ethyl alcohol.

Drew et al.: J. A. C. 8., vol. 61, p. 2666 (1939). Long et al.: J. A. C. 8., vol. 63, pp. 1586-9 (1941). 

1. A-(2,4,6-TRILODOPHENOXY) BUTYRIC ACID. 